TY - JOUR T1 - Revisiting the loading dose of amikacin for patients with severe sepsis and septic shock90 JF - Crit Care Y1 - 2010 A1 - Taccone,F.S. A1 - Laterre,P.F. A1 - Spapen,H. A1 - Dugernier,T. A1 - I. Delattre A1 - Layeux,B. A1 - D. de Backer A1 - Wittebole,X. A1 - P.E. Wallemacq A1 - Vincent,J.L. A1 - Jacobs,F. KW - 0 KW - a KW - administration & dosage KW - Aged KW - Agent KW - Agents KW - ALL KW - Amikacin KW - an KW - Anti-Bacterial Agents KW - article KW - AS KW - Belgian KW - Belgium KW - blood KW - Body weight KW - Body-weight KW - Bruxelles KW - care KW - Clinical KW - clinical trial KW - conditions KW - Correlation KW - data KW - de KW - Diagnosis KW - distribution KW - Dose-Response Relationship,Drug KW - doses KW - electronic KW - Enterobacteriaceae KW - Female KW - Fluorescence KW - Fluorescence Polarization Immunoassay KW - Half-Life KW - hospital KW - Humans KW - im KW - Immunoassay KW - intensive care KW - intensive care unit KW - intensive care units KW - IS KW - IT KW - journal KW - LEVEL KW - levels KW - Male KW - method KW - methods KW - middle aged KW - MODEL KW - Monitoring KW - Patient KW - patients KW - Pharmacokinetic KW - pharmacokinetics KW - pharmacology KW - physiopathology KW - Prospective Studies KW - Pseudomonas KW - Pseudomonas aeruginosa KW - Research KW - Research Support KW - result KW - results KW - Sample KW - Samples KW - SB - IM KW - Sepsis KW - serum KW - Severity of Illness Index KW - Shock,Septic KW - study KW - Target KW - Therapy KW - time KW - Times KW - treatment KW - VARIABILITY KW - Volume KW - Weight AB - INTRODUCTION: It has been proposed that doses of amikacin of >15 mg/kg should be used in conditions associated with an increased volume of distribution (Vd), such as severe sepsis and septic shock. The primary aim of this study was to determine whether 25 mg/kg (total body weight) of amikacin is an adequate loading dose for these patients. METHODS: This was an open, prospective, multicenter study in four Belgian intensive care units (ICUs). All consecutive patients with a diagnosis of severe sepsis or septic shock, in whom amikacin treatment was indicated, were included in the study. RESULTS: In 74 patients, serum samples were collected before (t = 0 h) and 1 hour (peak), 1 hour 30 minutes, 4 hours 30 minutes, 8 hours, and 24 hours after the first dose of amikacin. Blood amikacin levels were measured by using a validated fluorescence polarization immunoassay method, and an open two-compartment model with first-order elimination was fitted to concentrations-versus-time data for amikacin (WinNonlin). In 52 (70%) patients, peak serum concentrations were >64 microg/ml, which corresponds to 8 times the clinical minimal inhibitory concentration (MIC) breakpoints defined by EUCAST for Enterobacteriaceae and Pseudomonas aeruginosa (S<8, R>16 microg/ml). Vd was 0.41 (0.29 to 0.51) L/kg; elimination half-life, 4.6 (3.2 to 7.8) hours; and total clearance, 1.98 (1.28 to 3.54) ml/min/kg. No correlation was found between the amikacin peak and any clinical or hemodynamic variable. CONCLUSIONS: As patients with severe sepsis and septic shock have an increased Vd, a first dose of >or= 25 mg/kg (total body weight) of amikacin is required to reach therapeutic peak concentrations. However, even with this higher amikacin dose, the peak concentration remained below therapeutic target levels in about one third of these patients. Optimizing aminoglycoside therapy should be achieved by tight serum-concentration monitoring because of the wide interindividual variability of pharmacokinetic abnormalities VL - 14 CP - 2 U1 - 38884 M3 - cc8945 [pii];10.1186/cc8945 [doi] ER -